on November 7, 2002
Published online before print November 7, 2002, doi: 10.1161/01.ATV.0000046235.22451.66
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Submitted on September 5, 2002
Accepted on November 17, 2002
Thrombospondin-2 Polymorphism Is Associated With a Reduced Risk of Premature Myocardial Infarction
S. Matthijs Boekholdt *;
From the Departments of Cardiology (S.M.B., M.D.T., R.J.G.P., M.E.), Clinical Epidemiology and Biostatistics (A.H.Z.), and Vascular Medicine (J.J.P.K.) and Laboratory for Experimental Internal Medicine (P.H.R.), Academic Medical Center, Amsterdam and the Department of Chronic Disease Epidemiology (J.M.A.B., E.J.M.F.), National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
* To whom correspondence should be addressed. E-mail: s.m.boekholdt{at}amc.uva.nl.
Objective—Recently, polymorphisms in thrombospondin (THBS) genes coding for THBS-1 (N700S), THBS-2 (T>G substitution in 3'-untranslated region), and THBS-4 (A387P) genes were proposed to modulate the risk of premature coronary artery disease (CAD) or myocardial infarction (MI). It was our objective to verify this hypothesis in an independent cohort.
Methods and Results—We performed a case-control study among patients (n=503) referred to our institution for symptomatic CAD that occurred before the age of 50 years and a group of age- and sex-matched population-based controls free of CAD (n=1071). The THBS-1 variant allele was not associated with an altered risk of premature CAD or MI. Homozygosity for the THBS-2 variant allele and the THBS-4 variant (387P) allele was significantly associated with a reduced risk of premature MI compared with wild-type individuals (OR=0.44, 0.24 to 0.84 and OR=0.43, 0.22 to 0.85, respectively). The latter observation is in contrast with a previous report, although confidence intervals overlap.
Conclusions—We conclude that a relationship between the THBS-1 N700S polymorphism and premature CAD is unlikely. For the THBS-4 A387P polymorphism, additional studies are required to elucidate its role in premature CAD. Finally, we conclude that the THBS-2 polymorphism is associated with a reduced risk of premature MI.
Key words: thrombospondin • polymorphism • premature coronary artery disease • premature myocardial infarction
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